BEMPEG With Pembrolizumab vs Pembrolizumab Alone in Patients With Metastatic or Recurrent HNSCC (PROPEL-36)

Phase 2

Terminated

• Conditions: Metastatic Head and Neck Cancer; Recurrent Head and Neck Cancer
• Interventions: Drug: Bempegaldesleukin; Drug: Pembrolizumab

• Registration Number: NCT04969861
• Lead Sponsor: Nektar Therapeutics

Brief Summary

This is a multicenter, randomized, open-label, Phase 2/3 study that will evaluate the efficacy and safety of bempegaldesleukin (BEMPEG; NKTR-214) combined with pembrolizumab compared with pembrolizumab monotherapy in patients with recurrent or metastatic HNSCC with positive PD-L1 expression (CPS ≥ 1).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-09
• Study First Submitted QC: 2021-07-09
• Study First Posted: 2021-07-21
• Study Start: 2022-03-09
• Primary Completion: 2022-04-22
• Study Completion: 2022-04-22
• Results First Submitted: 2022-10-24
• Status Verified: 2022-11
• Results First Submitted QC: 2022-11-21
• Results First Posted: 2022-12-15
• Last Update Submitted: 2022-12-16
• Last Update Posted: 2023-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

• Provide written, informed consent to participate in the study and follow the study procedures.

• Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).

• Have histologically or cytologically-confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies.

  • No prior systemic therapy for recurrent or metastatic disease.
  • The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
  • Patients may not have a primary tumor site of nasopharynx (any histology) and/or unknown primary.

• Have measurable disease based on RECIST 1.1 as determined by the local site Investigator.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Measure Description: GRADE - ECOG PERFORMANCE STATUS

0 - Fully active, able to carry on all pre-disease performance without restriction

1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work

2- Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours

• The tumor must have positive PD-L1 expression (i.e., CPS ≥1)

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Exclusion Criteria

• Has disease that is suitable for local therapy administered with curative intent.
• Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
• Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to initiation of study drug
• Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) as determined by the Investigator.
• Has a known additional malignancy that is progressing or has required active treatment within 5 years prior to the first dose of study drug
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
• Use of an investigational agent or an investigational device within 28 days before the first dose of study drug.
• Prior treatment with an anti PD-1, anti PD-L1, anti-PD-L2, or anti CTLA-4 antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.

NOTE: Other protocol defined inclusion/exclusion criteria may apply

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BEMPEG + Pembrolizumab	Bempegaldesleukin	Bempegaldesleukin plus pembrolizumab every 3 weeks (q3w) for up to 35 cycles (approximately 2 years).
BEMPEG + Pembrolizumab	Pembrolizumab	Bempegaldesleukin plus pembrolizumab every 3 weeks (q3w) for up to 35 cycles (approximately 2 years).
Pembrolizumab Monotherapy	Pembrolizumab	Pembrolizumab monotherapy q3w for up to 35 cycles (approximately 2 years).

Primary Outcome Measures

Name	Time	Method
Overall Survival	Approximately 2 years
Objective Response Rate	Approximately 2 years	To compare the objective response rate (ORR) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival	Approximately 2 years	To compare progression-free survival (PFS) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.
Time to Deterioration	Approximately 2 years	The time from baseline to a ≥ 10-point decrease with confirmation by the subsequent visit of a ≥ 10-point deterioration from baseline in: • Global health status/quality of life assessment based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30).; The EORTC QLQ-C30 is a 30-item questionnaire designed to assess the quality of life of cancer patients. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning.; • Pain and Swallowing based on respective multi-item scales of EORTC QLQ head and neck cancer specific module (EORTC QLQ-H\&N35).; EORTC QLQ-H\&N35 consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates increased severity of symptoms.
Change in Global Health Status/Quality of Life	Approximately 2 years	To compare mean change from baseline in global health status/quality of life scale of EORTC QLQ-C30. The EORTC QLQ-C30 is composed of multi-item scales and single item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), a global health status/HRQoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning.
Percentage of Patients With Treatment-Emergent Adverse Events and Serious Adverse Events	Screening baseline through end of study, approximately 2 years	Compare the overall safety and tolerability based on assessments of treatment-emergent adverse events and serious adverse events

Trial Locations

Locations (4)

Universitätsklinikum Salzburg, Landeskrankenhaus,; 🇦🇹 Salzburg, Salzburg Bundesland, Austria

Attikon University General Hospital; 🇬🇷 Athens, Attiki, Greece

Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

ASST Degli Spedali Civili di Brescia; 🇮🇹 Brescia, Lombardia, Italy